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141.
Andrei Ogrel Alexei Ogrel Svetlana Ogrel Vitaliy Shvets Jan Raap 《International journal of peptide research and therapeutics》1998,5(2-3):175-178
Summary Synthesis of zervamicin IIB, specifically labeled at the α-position of glutamine-11 with15N, was achieved by the Fmoc/tert.-butyl strategy in solution using a fragment condensation approach. Three fragments of zervamicin IIB were obtained by stepwise
elongation with Fmoc amino acids using BOP as a coupling reagent. For the introduction of the highly sterically hindered α-aminoisobutyric
acid residues, BOP/DMAP activation was applied. Peptide fragments were coupled by means of the coupling reagent, CF3-PyBOP. Using the strategy developed, zervamicin IIB specifically15N labeled has been synthesized in 30% overall yield based on the isotopically labeled amino acid. From 600 MHz NMR spectroscopy
the position of the15N-label was clearly detected. The isotope enrichment (98 ±2%) was determined by FAB-mass spectrometry. 相似文献
142.
Senescence-induced RNases in tomato 总被引:18,自引:0,他引:18
143.
Andrei A. Gakh Natalia Yu Anisimova Mikhail V. Kiselevsky Sergey V. Sadovnikov Ivan N. Stankov Mikhail V. Yudin Konstantin A. Rufanov Mikhail Yu Krasavin Andrey V. Sosnov 《Bioorganic & medicinal chemistry letters》2010,20(20):6149-6151
Dihydro-resveratrol (dihydro-R), a prominent polyphenol component of red wine, has a profound proliferative effect on hormone-sensitive tumor cell lines such as breast cancer cell line MCF7. We found a significant increase in MCF7 tumor cells growth rates in the presence of picomolar concentrations of this compound. The proliferative effect of dihydro-R was not observed in cell lines that do not express hormone receptors (MDA-MB-231, BT-474, and К-562). 相似文献
144.
Franziska R?mmler Monika Hammel Anna Waldhuber Tina Müller Marion Jurk Eugen Uhlmann Hermann Wagner J?rg Vollmer Thomas Miethke 《PloS one》2015,10(2)
Activation of TLR7 and TLR9 by endogenous RNA- or DNA-containing ligands, respectively, is thought to contribute to the complicated pathophysiology of systemic lupus erythematosus (SLE). These ligands induce the release of type-I interferons by plasmacytoid dendritic cells and autoreactive antibodies by B-cells, both responses being key events in perpetuating SLE. We recently described the development of inhibitory oligonucleotides (INH-ODN), which are characterized by a phosphorothioate backbone, a CC(T)XXX3–5GGG motif and a chemical modification of the G-quartet to avoid the formation of higher order structures via intermolecular G-tetrads. These INH-ODNs were equally or significantly more efficient to impair TLR7- and TLR9-stimulated murine B-cells, macrophages, conventional and plasmacytoid dendritic cells than the parent INH-ODN 2088, which lacks G-modification. Here, we evaluate the inhibitory/therapeutic potential of our set of G-modified INH-ODN on human immune cells. We report the novel finding that G-modified INH-ODNs efficiently inhibited the release of IFN-α by PBMC stimulated either with the TLR7-ligand oligoribonucleotide (ORN) 22075 or the TLR9-ligand CpG-ODN 2216. G-modification of INH-ODNs significantly improved inhibition of IL-6 release by PBMCs and purified human B-cells stimulated with the TLR7-ligand imiquimod or the TLR9-ligand CpG-ODN 2006. Furthermore, inhibition of B-cell activation analyzed by expression of activation markers and intracellular ATP content was significantly improved by G-modification. As observed with murine B-cells, high concentrations of INH-ODN 2088 but not of G-modified INH-ODNs stimulated IL-6 secretion by PBMCs in the absence of TLR-ligands thus limiting its blocking efficacy. In summary, G-modification of INH-ODNs improved their ability to impair TLR7- and TLR9-mediated signaling in those human immune cells which are considered as crucial in the pathophysiology of SLE. 相似文献
145.
Kimberley J. Evason Macrina T. Francisco Vladislava Juric Sanjeev Balakrishnan Maria del Pilar Lopez Pazmino John D. Gordan Sanjay Kakar Jan Spitsbergen Andrei Goga Didier Y. R. Stainier 《PLoS genetics》2015,11(7)
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. The search for targeted treatments has been hampered by the lack of relevant animal models for the genetically diverse subsets of HCC, including the 20-40% of HCCs that are defined by activating mutations in the gene encoding β-catenin. To address this chemotherapeutic challenge, we created and characterized transgenic zebrafish expressing hepatocyte-specific activated β-catenin. By 2 months post fertilization (mpf), 33% of transgenic zebrafish developed HCC in their livers, and 78% and 80% of transgenic zebrafish showed HCC at 6 and 12 mpf, respectively. As expected for a malignant process, transgenic zebrafish showed significantly decreased mean adult survival compared to non-transgenic control siblings. Using this novel transgenic model, we screened for druggable pathways that mediate β-catenin-induced liver growth and identified two c-Jun N-terminal kinase (JNK) inhibitors and two antidepressants (one tricyclic antidepressant, amitriptyline, and one selective serotonin reuptake inhibitor) that suppressed this phenotype. We further found that activated β-catenin was associated with JNK pathway hyperactivation in zebrafish and in human HCC. In zebrafish larvae, JNK inhibition decreased liver size specifically in the presence of activated β-catenin. The β-catenin-specific growth-inhibitory effect of targeting JNK was conserved in human liver cancer cells. Our other class of hits, antidepressants, has been used in patient treatment for decades, raising the exciting possibility that these drugs could potentially be repurposed for cancer treatment. In support of this proposal, we found that amitriptyline decreased tumor burden in a mouse HCC model. Our studies implicate JNK inhibitors and antidepressants as potential therapeutics for β-catenin-induced liver tumors. 相似文献
146.
Elizabeth Peacock Sarah A. Sonsthagen Martyn E. Obbard Andrei Boltunov Eric V. Regehr Nikita Ovsyanikov Jon Aars Stephen N. Atkinson George K. Sage Andrew G. Hope Eve Zeyl Lutz Bachmann Dorothee Ehrich Kim T. Scribner Steven C. Amstrup Stanislav Belikov Erik W. Born Andrew E. Derocher Ian Stirling Mitchell K. Taylor ?ystein Wiig David Paetkau Sandra L. Talbo 《PloS one》2015,10(8)
147.
Rafael Laboissière Jean-Charles Letievant Eugen Ionescu Pierre-Alain Barraud Michel Mazzuca Corinne Cian 《PloS one》2015,10(12)
Motion sickness (MS) usually occurs for a narrow band of frequencies of the imposed oscillation. It happens that this frequency band is close to that which are spontaneously produced by postural sway during natural stance. This study examined the relationship between reported susceptibility to motion sickness and postural control. The hypothesis is that the level of MS can be inferred from the shape of the Power Spectral Density (PSD) profile of spontaneous sway, as measured by the displacement of the center of mass during stationary, upright stance. In Experiment 1, postural fluctuations while standing quietly were related to MS history for inertial motion. In Experiment 2, postural stability measures registered before the onset of a visual roll movement were related to MS symptoms following the visual stimulation. Study of spectral characteristics in postural control showed differences in the distribution of energy along the power spectrum of the antero-posterior sway signal. Participants with MS history provoked by exposure to inertial motion showed a stronger contribution of the high frequency components of the sway signal. When MS was visually triggered, sick participants showed more postural sway in the low frequency range. The results suggest that subject-specific PSD details may be a predictor of the MS level. Furthermore, the analysis of the sway frequency spectrum provided insight into the intersubject differences in the use of postural control subsystems. The relationship observed between MS susceptibility and spontaneous posture is discussed in terms of postural sensory weighting and in relation to the nature of the provocative stimulus. 相似文献
148.
Andrei V. Chaplin Boris A. Efimov Vladimir V. Smeianov Lyudmila I. Kafarskaia Alla P. Pikina Andrei N. Shkoporov 《PloS one》2015,10(8)
Members of genus Bifidobacterium are Gram-positive bacteria, representing a large part of the human infant microbiota and moderately common in adults. However, our knowledge about their diversity, intraspecific phylogeny and long-term persistence in humans is still limited. Bifidobacterium longum is generally considered to be the most common and prevalent species in the intestinal microbiota. In this work we studied whole genome sequences of 28 strains of B. longum, including 8 sequences described in this paper. Part of these strains were isolated from healthy children during a long observation period (up to 10 years between isolation from the same patient). The three known subspecies (longum, infantis and suis) could be clearly divided using sequence-based phylogenetic methods, gene content and the average nucleotide identity. The profiles of glycoside hydrolase genes reflected the different ecological specializations of these three subspecies. The high impact of horizontal gene transfer on genomic diversity was observed, which is possibly due to a large number of prophages and rapidly spreading plasmids. The pan-genome characteristics of the subspecies longum corresponded to the open pan-genome model. While the major part of the strain-specific genetic loci represented transposons and phage-derived regions, a large number of cell envelope synthesis genes were also observed within this category, representing high variability of cell surface molecules. We observed the cases of isolation of high genetically similar strains of B. longum from the same patients after long periods of time, however, we didn’t succeed in the isolation of genetically identical bacteria: a fact, reflecting the high plasticity of microbiota in children. 相似文献
149.
Matheus Bertanha Andrei Moroz Rodrigo G. Jaldin Regina A.M. Silva Jaqueline C. Rinaldi Márjorie A. Golim Sérgio L. Felisbino Maria A.C. Domingues Marcone L. Sobreira Patricia P. Reis Elenice Deffune 《Experimental cell research》2014
Clinical experience for peripheral arterial disease treatment shows poor results when synthetic grafts are used to approach infrapopliteal arterial segments. However, tissue engineering may be an option to yield surrogate biocompatible neovessels. Thus, biological decellularized scaffolds could provide natural tissue architecture to use in tissue engineering, when the absence of ideal autologous veins reduces surgical options. The goal of this study was to evaluate different chemical induced decellularization protocols of the inferior vena cava of rabbits. They were decellularized with Triton X100 (TX100), sodium dodecyl sulfate (SDS) or sodium deoxycholate (DS). Afterwards, we assessed the remaining extracellular matrix (ECM) integrity, residual toxicity and the biomechanical resistance of the scaffolds. Our results showed that TX100 was not effective to remove the cells, while protocols using SDS 1% for 2 h and DS 2% for 1 h, efficiently removed the cells and were better characterized. These scaffolds preserved the original organization of ECM. In addition, the residual toxicity assessment did not reveal statistically significant changes while decellularized scaffolds retained the equivalent biomechanical properties when compared with the control. Our results concluded that protocols using SDS and DS were effective at obtaining decellularized scaffolds, which may be useful for blood vessel tissue engineering. 相似文献
150.
Matthew J Smith W Rod Hardy Guang‐Yao Li Marilyn Goudreault Steven Hersch Pavel Metalnikov Andrei Starostine Tony Pawson Mitsuhiko Ikura 《The EMBO journal》2010,29(5):884-896
Adaptor proteins respond to stimuli and recruit downstream complexes using interactions conferred by associated protein domains and linear motifs. The ShcA adaptor contains two phosphotyrosine recognition modules responsible for binding activated receptors, resulting in the subsequent recruitment of Grb2 and activation of Ras/MAPK. However, there is evidence that Grb2‐independent signalling from ShcA has an important role in development. Using mass spectrometry, we identified the multidomain scaffold IQGAP1 as a ShcA‐interacting protein. IQGAP1 and ShcA co‐precipitate and are co‐recruited to membrane ruffles induced by activated receptors of the ErbB family, and a reduction in ShcA protein levels inhibits the formation of lamellipodia. We used NMR to characterize a direct, non‐canonical ShcA PTB domain interaction with a helical fragment from the IQGAP1 N‐terminal region that is pTyr‐independent. This interaction is mutually exclusive with binding to a more conventional PTB domain peptide ligand from PTP–PEST. ShcA‐mediated recruitment of IQGAP1 may have an important role in cytoskeletal reorganization downstream of activated receptors at the cell surface. 相似文献